History Of Clinical Cardiovascular Disease Research Articles

Association of silent myocardial infarction on electrocardiogram and coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis.

Silent myocardial infarction (SMI) on electrocardiogram (ECG) is associated with atherosclerotic cardiovascular disease, but the relationship between SMI on ECG and coronary artery calcium (CAC) remains poorly understood. Characterize the relationship between SMI on ECG and CAC. Eligible participants from the Multi-Ethnic Study of Atherosclerosis study had ECG and CAC scoring at study enrollment (2000-2002). SMI was defined as ECG evidence of myocardial infarction in the absence of a history of clinical cardiovascular disease. CAC was modeled both continuously and categorically. The cross-sectional relationships between SMI on ECG and CAC were assessed using logistic regression and linear regression. Among 6705 eligible participants, 178 (2.7%) had baseline SMI. Compared to participants without SMI, those with SMI had higher CAC (median [IQR]: 61.2 [0-261.7] vs. 0 [0-81.5]; p < .0001). Participants with SMI were more likely to have non-zero CAC (74% vs. 49%) and were more likely to have CAC ≥ 100 (40% vs. 23%). In a multivariable-adjusted logistic model, SMI was associated with higher odds of non-zero CAC (odds ratio 2.17, 95% CI 1.48-3.20, p < .0001) and 51% higher odds of CAC ≥ 100 (odds ratio 1.51, 95% CI 1.06-2.16, p = .02). An incidental finding of SMI on ECG may serve to identify patients who have a higher odds of significant CAC and may benefit from additional risk stratification to further refine their cardiovascular risk. Further exploration of the utility of CAC assessment in this patient population is needed.

Statins for extension of disability-free survival and primary prevention of cardiovascular events among older people: protocol for a randomised controlled trial in primary care (STAREE trial)

IntroductionThe world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these...

Association between plasma desmosine, a marker of elastin degradation, and total atherosclerotic burden measured by whole body magnetic resonance angiography

Abstract Background Elastin degradation has been implicated in the pathophysiology of vulnerable atherosclerotic plaque. Desmosine is the cross-link component in the elastin molecule and is exclusively released from mature elastin breakdown, thus has the potential to be a physiologically relevant biomarker of atherosclerosis. Objectives The aim of the present study was: 1. To investigate whether patients with known cardiovascular disease (CVD) have higher elastin degradation as indicated by plasma desmosine (pDES); 2. to determine the relationship between pDES and total atherosclerotic burden. Methods We measured pDES by a validated stable isotope dilution LC-MS/MS method1 in a total of 146 subjects from the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study2. (62% male, mean age 64±8 (SD) years). This included 62 patients with prior clinical diagnosis of CVD (including coronary artery disease (CAD), cerebrovascular disease and/or lower extremity arterial disease (LEAD)), and 84 patients without a clinical diagnosis of CVD. Total atherosclerotic burden was measured by whole body magnetic resonance angiography (WB-MRA). The WB-MRA data was divided into 31 anatomical arterial segments with each segment scored according to degree of luminal narrowing: 0 = no stenosis, 1 = &amp;lt;50% stenosis, 2 = 51–70% stenosis, 3 = 71–99% stenosis, 4 = vessel occlusion. The segment scores were summed and from this, a standardized atheroma score (SAS) was calculated by summing each individual segment's stenosis score, and divided by the number of diagnostic segments before dividing by 4 which is the maximum potential score. Relationship between SAS and pDES levels was investigated using multiple linear regression models Results pDES levels were significantly greater in patients with established clinical CVD compared to patients with no CVD (CVD patients, 0.56 (0.45–0.67) ng/mL; patients with no CVD, 0.47 (0.41–0.54)ng/mL; p=0.001). Median SAS for the study population was 4 (2–10). Overall pDES levels showed a strong correlation with SAS (r=0.44, p≤0.001). Univariable analysis suggested a significant association between pDES and whole-body atheroma score as measured by SAS. (β 29.31, p&amp;lt;0.001). This association persisted in the multivariable regression model adjusting for traditional cardiovascular risk factors including age, gender, BMI, systolic blood pressure, diabetes, smoking status and LDL. (adjusted β 18.75, p=0.004) Conclusion pDES levels are elevated in patients with clinical CVD when compared to those with no clinical history of CVD. pDES is also strongly associated with global atheroma burden. Overall, these findings support the role of pDES as a potential biomarker for atherosclerosis. Funding Acknowledgement Type of funding sources: None.

Elevated NT-ProBNP as a Cardiovascular Disease Risk Equivalent: Evidence from the Atherosclerosis Risk in Communities (ARIC) Study

BackgroundIt remains unclear whether elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) can serve as a “risk equivalent” for cardiovascular disease to adults at high cardiovascular risk. MethodsWe included 9789 participants (mean age 63.2 years, 55% women, 19.4% Black, 13% with a history of cardiovascular disease) who attended Atherosclerosis Risk in Communities Study Visit 4 (1996-1998). We classified participants as having a history of cardiovascular disease at baseline and, among those without cardiovascular disease, we defined categories of NT-proBNP (<125, 125-449, ≥450 pg/mL). We used Cox regression to estimate associations of NT-proBNP with incident cardiovascular disease and mortality. ResultsOver a median 20.5 years of follow-up, there were 4562 deaths (917 cardiovascular deaths). There were 2817 first events and 806 recurrent events (in those with a history of cardiovascular disease at baseline). Among individuals without a history of cardiovascular disease, those adults with NT-proBNP ≥450 pg/mL had significantly higher risks of all-cause death (hazard ratio [HR] 2.12; 95% confidence interval [CI], 1.78-2.53), cardiovascular mortality (HR 2.92; 95% CI, 2.15-3.97), incident total cardiovascular disease (HR 2.59; 95% CI, 2.13-3.16), atherosclerotic cardiovascular disease (HR 2.20; 95% CI, 1.72-2.80), and heart failure (HR 3.81; 95% CI, 3.01-4.81), compared with individuals with NT-proBNP <125 pg/mL. The elevated cardiovascular risk in persons with high NT-proBNP and no history of cardiovascular disease was similar to, or higher than, the risk conferred by a history of cardiovascular disease. ConclusionsOur findings suggest that it might be appropriate to manage adults with NT-proBNP ≥450 pg/mL as if they had a history of clinical cardiovascular disease.

Altered cardiovascular health in COVID-19 patients

Mortality due to cardiac cause is common amongst COVID-19 patients. Myocarditis, decompensated heart failure, acute coronary syndrome, sinus tachycardia, atrial fibrillation and right bundle branch block (RBBB) were noted2 in many hospitalized COVID patients. Studies conducted time to time, in various countries and hospitals registered various numbers and percentages (%) of patients suffering from myocardial injury ranging from 8% to70% among the COVID victims. Infection by COVID-19 causes fever and inflammation in many organs and may cause serious myocarditis, even in those with no previous clinical history of cardiovascular disease.4 This infection may cause cardiomyopathy, altered rhythm, and reduction in optimum cardiac output.

Diabetic Retinopathy and Skin Tissue Advanced Glycation End Products Are Biomarkers of Cardiovascular Events in Type 2 Diabetic Patients.

Risk of cardiovascular events is not homogeneous in subjects with type 2 diabetes; therefore, its early identification remains a challenge to be met. The aim of this study is to evaluate whether the presence of diabetic retinopathy and accumulation of advanced glycation end-products in subcutaneous tissue can help identify patients at high risk of cardiovascular events. For this purpose, we conducted a prospective study (mean follow-up: 4.35 years) comprising 200 subjects with type 2 diabetes with no history of clinical cardiovascular disease and 60 non-diabetic controls matched by age and sex. The primary outcome was defined as the composite of myocardial infarction, coronary revascularization, stroke, lower limb amputation or cardiovascular death. The Cox proportional hazard multiple regression analysis was used to determine the independent predictors of cardiovascular events. The patients with type 2 diabetes had significantly more cardiovascular events than the non-diabetic subjects. Apart from the classic factors such as age, sex and coronary artery calcium score, we observed that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue were independent predictors of cardiovascular events. We conclude that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue could be useful biomarkers for selecting type 2 diabetic patients in whom the screening for cardiovascular disease should be prioritized, thereby creating more personalized and cost-effective medicine.

Abstract 9305: Association of Silent Myocardial Infarction on Electrocardiogram and Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis

Introduction: Silent myocardial infarction (SMI) on electrocardiogram (ECG) is associated with atherosclerotic cardiovascular disease, but the relationship between SMI on ECG and coronary artery calcium (CAC) remains poorly understood. Hypothesis: SMI on ECG is predictive of elevated CAC. Methods: Eligible participants from the Multi-Ethnic Study of Atherosclerosis (MESA) had ECG and CAC scoring at study enrollment (2000-2002). SMI was defined as ECG evidence of myocardial infarction in the absence of a history of clinical cardiovascular disease. CAC was modeled both continuously and categorically. The cross-sectional relationships between SMI on ECG and CAC were assessed using logistic regression and linear regression. Results: Among 6,705 eligible participants, 178 (2.7%) had baseline SMI. Compared to participants without SMI, those with SMI had higher CAC (median [IQR]: 61.2 [0 - 261.7] vs. 0 [0 - 81.5]; p &lt; 0.0001). Participants with SMI were more likely to have non-zero CAC (74% vs. 49%) and were more likely to have CAC ≥ 100 (40% vs. 23%). In a multivariable-adjusted logistic model, SMI was associated with higher odds of non-zero CAC (odds ratio 2.17, 95% CI 1.48 - 3.20, p &lt; 0.0001) and 51% higher odds of CAC ≥ 100 (odds ratio 1.51, 95% CI 1.06 - 2.16, p = 0.02). Conclusions: An incidental finding of SMI on ECG may serve to identify patients who have a higher odds of significant CAC and may benefit from additional risk-stratification to further refine their cardiovascular risk. Further exploration of the utility of CAC assessment in this patient population is needed.

Usefulness of skin advanced glycation end products to predict coronary artery calcium score in patients with type 2 diabetes.

The early identification of type 2 diabetic (T2D) patients at risk of developing coronary artery disease (CAD) remains a challenge. The coronary artery calcium score (CACs) is considered the most sensitive tool for assessing CAD risk in diabetic population, and the identification of a more targeted population in which the CACs would be more cost-efficient seems warranted. The accumulation of advanced glycation end products plays an important role in the pathogenesis of cardiovascular disease (CVD) in patients with diabetes. The aim of this study was to evaluate whether the assessment of skin autofluorescence (SAF) could be useful tool to identify those diabetic patients in whom CACs assessment should be prioritized. Prospective case-control study, comprising 156 subjects with T2D with no history of clinical CVD and 52 non-diabetic subjects matched by age. A value of CACs ≥ 400 Agatston Units (AU) was considered as "high CVD risk." Logistic regression analysis to predict a CACs ≥ 400 AU was performed. Sensibility and specificity were calculated using the optimal cutoff point based on ROC curve. T2D patients had higher value of SAF compared to controls (p = 0.011). Among subjects with diabetes, 122 presented CACs < 400 AU and 35 CACs ≥ 400 AU. SAF values were significantly higher among the group with CACs ≥ 400AU compared to patients with CACs < 400 (2.96 ± 0.86 vs. 2.59 ± 0.57; p = 0.0035). The logistic regression analysis showed that age, HDL-cholesterol and SAF values were independently related to CACs ≥ 400UA. Our finding suggests that SAF could be useful in selecting T2D patients in whom the screening for CAD by means of CACs assessment would be more cost-effective.

Rationale and Design of a Cluster Randomized Trial of a Village Doctor-Led Intervention on Hypertension Control in China.

In China, hypertension prevalence is high and increasing while the control rate is low, especially in rural areas. Traditionally, village doctors play an important role in infectious disease control and delivering essential health services to rural residents. We aim to test the effectiveness of a village doctor-led multifaceted intervention compared with usual care on blood pressure (BP) control and cardiovascular disease (CVD) among rural residents with hypertension in China. In the China Rural Hypertension Control Project (CRHCP), a cluster randomized trial, 163 villages were randomly assigned to the village doctor-led intervention and 163 villages to control. A total of 33,995 individuals aged ≥40 years with an untreated BP ≥140/90 mm Hg or treated BP ≥130/80 mm Hg or with an untreated BP ≥130/80 mm Hg and a history of clinical CVD were recruited into the study. The village doctor-led multifaceted intervention is designed to overcome barriers at the healthcare system, provider, patient, and community levels. Village doctors receive training on standard BP measurement, protocol-based hypertension treatment, and health coaching. They also receive technical support and supervision from hypertension specialists/primary care physicians and performance-based financial incentives. Study participants receive health coaching on home BP monitoring, lifestyle changes, and adherence to medications. The primary outcome is BP control (<130/80 mm Hg) at 18 months in phase 1 and CVD events over 36 months in phase 2. The CRHCP will provide critically important data on the effectiveness, implementation, and sustainability of a hypertension control strategy in rural China for reducing the BP-related CVD burden. Trial Number NCT03527719.

Total plaque area and plaque echogenicity are novel measures of subclinical atherosclerosis in patients with systemic lupus erythematosus.

Patients with SLE have an increased risk of developing cardiovascular disease (CVD). Multiple studies have shown that these patients have increased numbers of carotid plaques and greater intima-media thickness (IMT) than healthy controls. Measures such as total plaque area (TPA) and plaque echogenicity may be more sensitive and more relevant to cardiovascular risk than presence of plaque and IMT alone. Our objective was to produce the first report of TPA and echogenicity in a population of patients with SLE. One hundred patients with SLE and no history of clinical CVD were recruited. Clinical, serological and treatment variables were recorded and serum was tested for antibodies to apolipoprotein A-1 and high-density lipoprotein. Both carotid and both femoral artery bifurcations of each patient were scanned to determine IMT, TPA and echogenicity of plaques. Univariable and multivariable statistical analyses were carried out to define factors associated with each of these outcomes. Thirty-six patients had carotid and/or femoral plaque. Increasing age was associated with presence of plaque and increased IMT. Triglyceride levels were associated with presence of plaque. Mean (s.d.) TPA was 60.8 (41.6) mm2. Patients taking prednisolone had higher TPA. Most plaques were echolucent, but increased echogenicity was associated with prednisolone therapy and persistent disease activity. TPA and plaque echogenicity in patients with SLE are associated with different factors than those associated with presence of plaque and IMT. Longitudinal studies may show whether these outcome measures add value in the management of cardiovascular risk in SLE.

Cardiovascular Health and Mitochondrial Function: Testing an Association.

Although mitochondrial dysfunction appears to be a contributing factor in the pathogenesis of cardiovascular and metabolic diseases, empirical data on this association are still lacking. This study evaluated whether mitochondrial oxidative capacity, as assessed by phosphorus magnetic resonance spectroscopy, was associated with cardiovascular risk, as estimated by the Framingham Risk Score (FRS), and with a clinical history of cardiovascular disease (CVD), in community-dwelling adults. A total of 616 subjects from the Baltimore Longitudinal Study of Aging (mean age 66 years) underwent a comprehensive clinical evaluation. Mitochondrial oxidative capacity in skeletal muscle was assessed as post-exercise phosphocreatine recovery time constant by phosphorus magnetic resonance spectroscopy. Multivariate regression models were employed to determine the cross-sectional association of mitochondrial oxidative capacity with FRS and history of CVD. Decreased mitochondrial oxidative capacity was strongly associated with higher FRS independent of age, body composition, and physical activity. Lower oxidative capacity was also associated with a history of positive of CVD and higher number of CVD events. We speculate that the observed association could reflect the effect of an excessive production of oxidative species by dysfunctional mitochondria. Furthermore, decreased energy production could hamper the functionality of heart and vessels. In turn, a malfunctioning cardiovascular apparatus could fail to deliver the oxygen necessary for optimal mitochondrial energy production, therefore creating a vicious cycle. Longitudinal studies are necessary to ascertain the directionality of the association and the eventual presence of common pathogenetic roots. In conclusion, mitochondria could represent an important target for intervention in cardiovascular health.

Abstract 13196: The Utility of Silent Myocardial Infarction on Electrocardiogram as an ASCVD Risk Enhancer for Primary Prevention: The Multi-Ethnic Study of Atherosclerosis

Introduction: The 2018 AHA/ACC cholesterol guidelines introduced a new list of markers called “risk enhancers” that, if present, confer an increased risk of atherosclerotic cardiovascular disease (ASCVD). Notably absent is silent myocardial infarction (SMI) on electrocardiogram (ECG), even though SMI has been shown to be associated with future ASCVD. Hypothesis: Adding SMI to the pooled cohort equation (PCE) will improve risk discrimination and classification in those with intermediate ASCVD risk (5 - 20% 10-year risk). Methods: SMI was defined as a major Q-wave abnormality or minor Q/QS waves in the setting of major ST-T abnormalities in the absence of history of clinical cardiovascular disease. Incident ASCVD events included myocardial infarction, coronary heart disease death, and fatal and non-fatal stroke. Results: Among 2,278 intermediate-risk MESA participants, 48 (2.1%) had SMI at baseline. Over 32,150 person-years (median 15.8), incident ASCVD events occurred in 297/2,230 (13%) of those without SMI and 13/48 (27%) of those with SMI. In a Cox proportional hazards model that was adjusted for calculated 10-year ASCVD risk based on the PCE, SMI was associated with increased risk of ASCVD (HR 2.22, 95% CI 1.27 - 3.87, p = 0.005). Adding SMI to the PCE did not improve discrimination, with areas under the receiver operating characteristic curves for models without and with SMI of 0.5812 and 0.5874, respectively (p-value for difference 0.22; Figure 1a). The net reclassification improvement for adding SMI as a risk enhancer to reclassify participants from intermediate-risk to high-risk was 0.0242 (95% CI 0.0011 - 0.0472, p = 0.04; Figure 1b). Conclusions: Our findings suggest that the prevalence of SMI is 2.1% among those without known clinical cardiovascular disease considered intermediate-risk by the pooled cohort equation. In our analysis, SMI only modestly improved classification of risk, suggesting that it may not be very useful as an ASCVD risk enhancer.

High-Sensitivity Cardiac Troponin I for Risk Stratification in Older Adults.

Traditional cardiovascular risk factors are less predictive in older age. High-sensitivity cardiac troponin I (hs-cTnI) is a marker of subclinical cardiomyocyte damage associated with cardiovascular risk in middle-aged adults. We hypothesized hs-cTnI would be indicative of mortality and cardiovascular risk beyond traditional cardiovascular risk factors in older adults and may be more discriminatory compared to hs-troponin T (hs-cTnT). Prospective cohort study. Population-based Atherosclerosis Risk in Communities (ARIC) Study. We included 5,876 ARIC participants at Visit 5 (2011-2013). We used Cox regression for the association of hs-cTnI categories (women: <4, 4-<10, ≥10 ng/ml; men: <6, 6-<12, ≥12 ng/ml, prevalent cardiovascular disease (CVD)) with mortality and incident CVD (atherosclerotic CVD [ASCVD]: coronary heart disease or stroke, or heart failure). Participants were ages 66 to 90, 23% black, 42% male, and 24% had prevalent CVD. There were 1,053 (321 CVD) deaths (median follow-up 6.3 years). Participants with elevated hs-cTnI and no CVD (7% of participants) had mortality risk similar to those with a history of CVD (55.6 vs 55.7 deaths/1,000 person-years, P = .99). After adjustment, elevated hs-cTnI and no CVD (hazard ratio (HR) = 2.38, 95% confidence interval (CI) = 1.85-3.06) and prevalent CVD (HR = 2.21, 95% CI = 1.90-2.57) remained associated with mortality, compared to low hs-cTnI and no CVD. Elevated hs-cTnI was independently associated with incident CVD (HR = 3.41, 95% CI = 2.58-4.51), ASCVD (HR = 2.02, 95% CI = 1.36-2.98), and heart failure (HR = 6.16, 95% CI = 4.24-8.95). The addition of hs-cTnI significantly improved C-statistics for all outcomes and added greater discrimination than hs-cTnT for cardiovascular mortality and incident heart failure. Hs-cTnI improves mortality and CVD risk stratification in older adults beyond traditional risk factors and improved model discrimination more than hs-cTnT for certain outcomes. Elevated hs-cTnI without CVD identifies a high-risk group with comparable mortality risk as those with a history of clinical CVD.

Dietary fish and ω-3 polyunsaturated fatty acids are associated with leukocyte ABCA1 DNA methylation levels.

A diet rich in fish and ω-3 polyunsaturated fatty acids (PUFAs) has been thought to reduce the risk for cardiovascular disease (CVD). The beneficial effects of fish oil and ω-3 PUFA on CVD can be mediated by epigenetic status of the genes associated with lipid metabolism and inflammation. The aim of this study was to investigate whether dietary fish and fatty acid (FA) intakes are associated with leukocyte ATP-binding cassette transporter A1 (ABCA1) DNA methylation levels in a Japanese population. This cross-sectional study included 298 adults (137 men and 161 women) without clinical history of CVD or cancer. The pyrosequencing method was used to measure leukocyte ABCA1 DNA methylation levels. Dietary fish and FA intakes were assessed based on the validated food frequency questionnaire. Mean ABCA1 DNA methylation levels were significantly lower in the highest fish intake groups (≥5-6/wk) compared with the lowest intake group (≤1-2/wk; P = 0.004). In multivariable linear regression analyses, higher dietary intake of ω-3 PUFAs and ω-3 highly unsaturated fatty acids was significantly associated with decreased levels of ABCA1 DNA methylation (P = 0.001 and 0.005); whereas no significant associations were seen between intake of dietary saturated fatty acid, monounsaturated fatty acid, and ω-6 PUFAs and ABCA1 DNA methylation. Higher dietary fish and ω-3 PUFA intake were associated with lower ABCA1 DNA levels in a Japanese population. The present results may bring potential insights on biological mechanisms underlying the protective effects of dietary fish and ω-3 PUFA intakes on CVD.

Private and Public Bariatric Surgery Trends in New Zealand 2004-2017: Demographics, Cardiovascular Comorbidity and Procedure Selection.

For bariatric surgery, patient selection, procedural choice and availability has changed over time internationally. We analysed the annual volume and location of bariatric surgery in New Zealand by demographic characteristics, clinical history and procedure. Patients who underwent bariatric procedures between 1 January 2004 and 31 December 2017 were identified through New Zealand hospitalisation records. Hospitalisation and medication data were used to indicate a clinical history of cardiovascular disease (CVD) and/or diabetes. Publicly funded intervention rate by ethnicity was calculated using year- and sex-specific ethnic population estimates and obesity prevalence statistics. This study included 9109 patients, undergoing gastric bypass (GB, n = 3323) and sleeve gastrectomy (SG, n = 5452) as the most common procedures. Nationally, annual bariatric surgery volume increased in the public sector, from 34 to 516 between 2004 and 2017, with a similar increase in available private sector figures. Public recipients were significantly more likely to have a history of diabetes (33.8% vs 14.4%) and/or CVD (9.0% vs 4.7%) than private recipients. Male recipients had higher prevalence of diabetes (29.9% vs 17.6%) and CVD (12.9% vs 4.1%) than female recipients. After adjustment for the adult population prevalence of morbid obesity, Pacific people had half the intervention rate of European and Māori. Bariatric surgery is increasing in frequency in New Zealand, with SG and GB being the most common procedures. Significant differences in patient characteristics exist between the public and private sectors. Ensuring equitable selection of publicly funded bariatric surgery candidates remains a challenge.

Diabetic retinopathy as an independent predictor of subclinical cardiovascular disease: baseline results of the PRECISED study

ObjectiveDetection of subclinical cardiovascular disease (CVD) has significant impact on the management of type 2 diabetes. We examined whether the assessment of diabetic retinopathy (DR) is useful for identifying patients...

89 - Optimizing Diabetes Management in Cardiology Clinics

The Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada have been updated to ensure that patients with clinical cardiovascular (CV) disease are being considered for agents that have shown CV benefit as a second-line agent for glycemic control. Our prospective observational study aimed to identify patients in a cardiology clinic with type 2 diabetes and a history of CV disease who were not on medications optimized for CV benefit. Once identified, these patients were either referred to endocrinologists or to their general practitioners for optimization consideration.

SERUM URIC ACID LEVELS ARE ASSOCIATED WITH ASYMPTOMATIC PERIPHERAL ARTERY DISEASE

Objective: Higher serum uric acid (SUA) levels have been implicated in the development and progression of atherosclerotic cardiovascular disease. However, it is not clear whether SUA levels are related to subclinical measures of cardiovascular disease, including peripheral arterial disease (PAD). The aim of our study was to test the association between increasing SUA levels and PAD in the Brisighella Heart Study Cohort. Design and method: A cross-sectional study was conducted among 974 participants to the 2012 Brisighella Heart Study aged more than 40 years, without clinical history of cardiovascular disease, type 2 diabetes or gout, and not treated with SUA lowering drugs. Main outcome-of-interest was PAD defined as ankle-brachial index less than 0.9 (n = 57). We used three models: the age (years), sex-adjusted model, multivariable model 1 additionally adjusted for smoking (never, former, current), alcohol intake (number of drinks/day), waist circumference (cm), hypertension (absent, present), and the multivariable model 2 further adjusted for LDL-C (mg/dL) and eGFR (EPI-CKD equation; ml/min) Results: Considering the whole cohort, a statistically significant inverse relation between uric acid level and ABI in the multivariable-adjusted model (beta [standard error] = −0.04 [0.009], p less than 0.001). This association was present in separate analyses among men and women. Higher SUA levels were positively associated with PAD, independent of smoking, body mass index (BMI), hypertension, serum LDL cholesterol, eGFR, and other confounders. Multivariable odds ratio (OR) [95 percent confidence intervals (CI)] comparing SUA levels higher than the 75th percentile (equal or more than 6 mg/dL) to uric acid levels less than the 50th percentile (less than 5.2 mg/dL) was 1.62 (1.08–2.44), p-trend = 0.015. This association persisted in separate analysis among men and women. Further, the results were consistent in subgroup analyses by categories of age, current smoking, BMI, and eGFR. Conclusions: Higher SUA levels are associated with PAD in non diabetic subjects in primary prevention for cardiovascular disease and gout.

Efficacy and safety of evolocumab in individuals with type 2 diabetes mellitus: primary results of the randomised controlled BANTING study

Aims/hypothesisThe study aimed to examine the efficacy of 12 weeks of monthly evolocumab or placebo in lowering LDL-cholesterol (LDL-C) in individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia and on a maximum-tolerated statin of at least moderate intensity.MethodsFor this randomised, placebo-controlled outpatient study, eligible individuals were ≥18 years old with type 2 diabetes, HbA1c <10% (86 mmol/mol), had been on stable pharmacological therapy for diabetes for ≥6 months and were taking a maximum-tolerated statin dose of at least moderate intensity. Lipid eligibility criteria varied by history of clinical cardiovascular disease. Participants were randomised 2:1 to evolocumab 420 mg s.c. or placebo. Randomisation was performed centrally via an interactive web-based or voice recognition system. Allocation was concealed using the centralised randomisation process. Treatment assignment was blinded to the sponsor study team, investigators, site staff and patients throughout the study. Co-primary endpoints were mean percentage change in LDL-C from baseline to week 12 and to the mean of weeks 10 and 12. Additional endpoints included LDL-C <1.81 mmol/l, LDL-C reduction ≥50% and other lipids. Exploratory analyses included percentage changes in fasting and post mixed-meal tolerance test (MMTT) lipoproteins and lipids, glucose metabolism variables and inflammatory biomarkers.ResultsIn total, 421 individuals were randomised and analysed, having received evolocumab (280 participants) or placebo (141 participants) (mean [SD] age 62 [8] years; 44% women; 77% white). Evolocumab decreased LDL-C by 54.3% (1.4%) at week 12 (vs 1.1% [1.9%] decrease with placebo; p < 0.0001) and by 65.0% (1.3%) at the mean of weeks 10 and 12 (vs 0.8% [1.8%] decrease with placebo; p < 0.0001); it also decreased non-HDL-cholesterol (HDL-C) by 46.9% (1.3%) at week 12 (vs 0.6% [1.8%] decrease with placebo) and by 56.6% (1.2%) at the mean of weeks 10 and 12 (vs 0.1% [1.6%] decrease with placebo). Evolocumab significantly improved levels of other lipids and allowed more participants to reach LDL-C <1.81 mmol/l or a reduction in LDL-C levels ≥50%. After an MMTT (120 min), there were favourable changes (p < 0.05; nominal, post hoc, no multiplicity adjustment) in chylomicron triacylglycerol (triglycerides), chylomicron cholesterol, VLDL-C and LDL-C. Evolocumab had no effect on glycaemic variables and was well tolerated.Conclusions/interpretationIn statin-treated individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia, evolocumab significantly reduced LDL-C and non-HDL-C. Favourable changes (p < 0.05) were observed in postprandial levels of chylomicrons, VLDL-C and LDL-C.Trial registrationClinicalTrials.gov NCT02739984FundingThis study was funded by Amgen Inc.Data availabilityQualified researchers may request data from Amgen clinical studies. Complete details are available at www.amgen.com/datasharing.

Serum osteopontin negatively impacts on intima‐media thickness in patients with systemic lupus erythematosus

Ultrasound evaluation of carotid intima-media thickness (cIMT) has been extensively used for potentially improving cardiovascular (CV) risk stratification in several patients' categories. Subjects with systemic lupus erythematosus (SLE) have been investigated by both imaging and molecular biomarker approaches with contrasting results. Here, we focused on the role of osteopontin (OPN) as biomarker of subclinical atherosclerosis associated with SLE. Eighty females (age 18-65years) affected by SLE and eighty age-matched healthy female controls without a clinical history of CV disease underwent ultrasound evaluation of cIMT and blood sample assay of high-sensitivity C-reactive protein (hs-CRP) and OPN. Healthy controls and SLE patients significantly differed for CV risk factors (ie, waist circumference, hypertension and dyslipidaemia) and the inflammatory status. Noteworthy, an opposite association between cIMT and OPN was observed in the two study groups. Whereas OPN was positively associated with mean cIMT (r=0.364; P=0.001) in SLE patients, a negative correlation was found in healthy controls. Furthermore, in SLE patients increased circulating levels of OPN were associated with the use of hydroxychloroquine and the positivity for the anti-dsDNA autoantibodies. At linear regression analysis, only OPN remained independently associated with cIMT also after adjustment for age, smoking pack-year, Heart SCORE, disease length and steroid therapy length. These results indicate that serum OPN levels were strongly associated with subclinical atherosclerosis in patients with LES and it might be a useful CV biomarker that requires additional validation in larger trials.